Figure 1.

Role of regulatory T cells in the context of filarial infection. Filarial parasite infective larvae (L3) deposited on the skin during the bite of an infective mosquito actively penetrate the skin following which they migrate to a draining lymph node. During their migration, L3 contacts and activates different cells such as keratinocytes (KC), dermal dendritic cells (dDC), innate lymphoid cells (ILCs), macrophages (MAC), dendritic cells (DCs), and basophils (Baso). At this relatively early phase of infection the parasite induces the differentiation of effector Th1, Th17, and Th2 cells, which together with IgE antibody may lead to attrition of some of the parasites. However if there is failure to clear the parasites, the infection evolves into a chronic longstanding infection associated with IL-10-producing type 1 (Tr1), TGF-β-producing Th3, and Foxp3-expressing Tregs or peripheral Tregs (pTregs), which together with the thymus-derived Tregs (tTregs) can be found with increasing frequencies in filarial infections. The high levels of IL-10 produced induce the production of IgG4 and together with IL-4, IL-13, and/or TGF-β induce the differentiation of alternatively activated macrophages (AAM) and inhibit the function of a variety of other cells.